Revealing electronic features governing hydrolysis of cephalosporins in the active site of the L1 metallo-β-lactamase.

ABSTRACT: The QM/MM simulations followed by electron density feature analysis are carried out to deepen the understanding of the reaction mechanism of cephalosporin hydrolysis in the active site of the L1 metallo-β-lactamase. The differences in reactivity of ten similar cephalosporin compounds are explained by using an extended set of bonding descriptors. The limiting step of the reaction is characterized by the proton transfer to the nitrogen atom of the cephalosporin thiazine ring accompanied with formation of the C₄[double bond, length as m-dash]C₃ double bond in its N-C₄-C₃ fragment. The temporary N⋯H-O_w hydrogen bond, which is formed in the transition state of the limiting step of the reaction was recognized as a key atomic interaction gove

SUBMITTER: Levina EO 

PROVIDER: S-EPMC9050041 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature